Synthesis of a Small Library of Nature-Inspired Xanthones and Study of Their Antimicrobial Activity

Abstract

A series of thirteen xanthones <b>3</b>-<b>15</b> was prepared based on substitutional (appendage) diversity reactions. The series was structurally characterized based on their spectral data and HRMS, and the structures of xanthone derivatives <b>1</b>, <b>7</b>, and <b>8</b> were determined by single-crystal X-ray diffraction. This series, along with an in-house series of aminated xanthones <b>1</b><b>6</b>-<b>33</b><b>,</b> was tested for in-vitro antimicrobial activity against seven bacterial (including two multidrug-resistant) strains and five fungal strains. 1-(Dibromomethyl)-3,4-dimethoxy-9<i>H</i>-xanthen-9-one (<b>7</b>) and 1-(dibromomethyl)-3,4,6-trimethoxy-9<i>H</i>-xanthen-9-one (<b>8</b>) exhibited antibacterial activity against all tested strains. In addition, 3,4-dihydroxy-1-methyl-9<i>H</i>-xanthen-9-one (<b>3</b>) revealed a potent inhibitory effect on the growth of dermatophyte clinical strains (<i>T. rubrum</i> FF5, <i>M.</i> <i>canis</i> FF1 and <i>E.</i> <i>floccosum</i> FF9), with a MIC of 16 µg/mL for all the tested strains. Compounds <b>3</b> and <b>26</b> showed a potent inhibitory effect on two <i>C. albicans</i> virulence factors: germ tube and biofilm formation.